The complexes of the intercalating drug actinomycin D and its derivatives (as well as selected related drugs) with nucleic acids will be studied by nuclear magnetic resonance, fluorescence, circular dichroism, and visible spectroscopic techniques. Both oligonucleotides as well as DNA (native and synthetic) will be used in order to determine the geometry of the complexes, the thermodynamics of complex formation, the kinetics of association and dissociation, and the relative preference of the drugs for binding to the various sequences of DNA. The cooperative and competitive binding of these drugs will be studied. Several derivatives of these drugs will also be studied in order to correlate the molecular and electronic structure of the drug molecules to the physical properties associated with complexation, and the in vivo physiological activity of the drugs.